Alpha-fetoprotein (AFP) synthesis has been described in the spleens of mice undergoing GVH reactions and is correlated with the appearance of immunosuppression in these tissues. Involved lymph nodes or spleens from patients with lymphomas also show AFP synthesis and immunosuppression (by PHA reactivity and mixed lymphocyte responder cells). Immunosuppression is reversible in that the cells cultured in vitro for 7 days become normally reactive and AFP is lost from the surface of the cell during the period of culture. Therefore, indirect evidence supports the thesis that AFP may be responsible for suppression in lymphomatous tissues. The cell which binds AFP in the murine system has been shown to be a subpopulation of light density T lymphocytes, but the cell type(s) producing this protein in GVH reactions and in the human lymphomas have not been defined. Studies of cancer-prone families have revealed a high incidence of circulating cells with surface AFP in individuals with malignancy (81%), in 1st degree relatives (63%), and in 2nd degree relatives (18%) but less than 1% in normal and spouse controls. AFP positive cells may occur in these families in the absence of any elevations of serum AFP. Thus, surface immunofluorescence for AFP may be a marker of malignant disease, at least in cancer-prone families. BIBLIOGRAPHIC REFERENCES: Keller, R.H., Summerskill, W.H.J., Geubel, A.P., Shorter, R.G. and Tomasi, T.B., Jr. Alpha-Fetoprotein and Suppression of Cell Mediated Immunity in Chronic Active Liver Disease (CALD). Gastroenterology 70:A-43/901, 1976. Calvanico, N.J., Dattwyler, R.J., Allen J.C. and Tomasi, T.B., Jr. The Effect of Bovine Amniotic Fluid Proteins on the Generation of Murine Cytotoxic T Cells. Fed. Proc. 35:250, 1976.